A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis

• Status: Completed
• Trial end date: 2017-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 2, randomized, double-blind, placebo- and active-controlled, parallel group, multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vertex Pharmaceuticals Incorporated
• Treatments: Ivacaftor

Criteria

Inclusion Criteria:

• Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.

• To prevent pregnancy, female participants of childbearing potential and their male partners will be required to use pre-specified, highly effective methods of non-hormonal contraception. Male participants with female partners of childbearing potential will be required to use a condom.

• Body weight ≥35 kg.

• Sweat chloride value ≥60 mmol/L from test results obtained during screening.

• Subjects must have an eligible CFTR genotype:

• Heterozygous for F508del and a minimal function (MF) mutation known or predicted not to be responsive to TEZ and/or IVA.

• Homozygous for F508del

• Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit

• Stable CF disease as judged by the investigator.

• Willing to remain on a stable CF medication regimen through the planned end of treatment or, if applicable, the Safety Follow up Visit.

Exclusion Criteria:

• History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.

• History of cirrhosis with portal hypertension.

• Risk factors for Torsade de Pointes

• History of hemolysis.

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.

• Clinically significant abnormal laboratory values at screening

• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.

• Lung infection with organisms associated with a more rapid decline in pulmonary status

• An acute illness not related to CF within 14 days before the first dose of study drug

• A standard digital ECG demonstrating QTc >450 msec at screening.

• History of solid organ or hematological transplantation.

• History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist based on the ophthalmologic examination during the Screening Period.

• History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.

• Ongoing or prior participation in an investigational drug study, with certain exceptions. (e.g., ongoing participation in NCT02565914)

• Use of commercially available CFTR modulator (e.g., Kalydeco, Orkambi) within 14 days before screening (applies only to the Heterozygous F508del/MF cohorts; does not apply to the Homozygous F508del/F508del Cohort).

• Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.